The filtration of a liquid sample by a membrane for purposes of purification (e.g., by removal of particulate or molecular contaminants) or concentration (e.g., for laboratory analysis) is a well developed art. Toward such ends, the flow of the liquid sample relative to the membrane's surface can in many instances be meaningfully characterized as either essentially parallel (i.e., tangential flow) or essentially normal (i.e., normal flow).
In a tangential flow filtration system, a large fraction of the liquid sample flows continuously, over time, in a direction essentially parallel to the membrane surface, as opposed to a much smaller portion which flows through the membrane. Because of the sweeping, cleansing nature of such flow—which discourages premature clogging, fouling, and concentration polarization—tangential flow filtration systems can often attain higher fluxes and higher throughputs than corresponding normal flow membrane filter systems. Because of these and other advantages, TFF systems are often pivotally employed for filtration in industrial drug manufacturing processes.
In the development of an industrial-scale drug filtration process there is often a need to timely investigate and qualify certain important parameters of the process, for example, its membrane characteristics, the flow path configuration and dynamics, the process' sequence of steps, and the allowable range of operating conditions. In drug development, timeliness is particularly important because a final “approved” manufacturing process often rests heavily upon its early foundations, and the parameters thereof can be “locked in”, for example, by early regulatory filings. The inability to adequately investigate filtration parameters can jeopardize yields, purity, membrane durability, etc., in the resulting industrial scale process, potentially delaying and/or frustrating commercialization.
Traditional methods of TFF process development require tedious, repetitive methodologies that, when performed manually, consume considerable time, and effort. There is need thus for an automatic process development device that a developer can use to design and run TFF processes on a laboratory scale and, in the course thereof, automatically collect and/or process information needed for “scaling up” the subject processes for industrial-scale operation.
Certain research entities have already established large engineering departments that, when needed, can custom design automated process development systems. However, the costs associated with such undertaking is often considerable, and seemingly, only research entities with vast in-house resources and expertise can successfully develop such custom-built APDS systems. These systems, moreover, tend to be “application-specific”, and consequently, have considerably limited commercial applicability.
Providing more flexible, more universal, and broader applicability in a single TFF process development device is problematic. Accommodating broad sample volume ranges, for example, is a particular concern, with both mechanical-and process-related issues being especially acute in the striking of an acceptable lower range (i.e., a minimum recirculation volume). Sample volumes in early process development stages—as is known—are often available only in minute quantities, and hence, cannot be squandered needlessly.
In light of the above—despite an existing need—there are currently no known automated TFF development devices capable of comprehensively acquiring meaningful developmental data, with a minimum sample volume requirement less than 20 ml.